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A special issue of Sensors entitled “Utilization of Electrochemical Sensors and Biosensors in Biochemistry and Molecular Biology” has been prepared over a period of three years. In this Editorial Note we would like to highlight one of the possible directions for electrochemical sensor and biosensor research resulting from the ideas of Czechoslovakian Nobel Prize winner Jaroslav Heyrovsky and his colleague Rudolf Brdicka.

Could electrochemistry be employed in biochemistry and molecular biology in the 21st century?

Cancer, “plague of the world”, is a word which brings to mind not only a threat to human health but also a subject of investigation for the broader scientific community (almost 60,000 papers appearing in Web of Science in 2007 included “cancer*” within their article titles, keywords or abstracts, and in particular, almost one hundred of them have been published in Nature). The success of treatment of the disease depends on many factors such as prevention, early and sensitive diagnostics. That means that the sooner a cancer is detected, the better the chances to treat it successfully. A very interesting idea about how we could diagnose a tumour disease was created seventy years ago in Czechoslovakia. This idea will not be forgotten.

Rudolf Brdicka, who was born one hundred years ago, published in Nature in 1937 his discoveries concerning the use of polarography to diagnose a tumour disease [1,2]. He discovered a sensitive polarographic “protein effect”, conspicuously exhibited by serum, which he explained as due to the catalytic activity of the sulphydryl groups of proteins. The “protein effect” consisted of the appearance of a characteristic wave on the current voltage curve, which was always found to be larger in normal serum samples than when the same procedure was applied to cancer serum [1,2]. A year ago Brdicka's colleague Jaroslav Heyrovsky, recipient of the 1959 Nobel Prize in Chemistry, published a paper in the same journal, where he summarized results obtained in the field of Polarographic Research on Cancer [3]. Heyrovsky believed that this field of study should be of general interest of many scientific groups around the world, but as it turns out he was apparently mistaken, as since then, electrochemistry has been slowly disappearing from tumour disease diagnostics due to the use of more modern analytical chemistry and molecular biology techniques. Thus, this unique and interesting technique has not been used, with several exceptions [4], for over fifty years.

Metallothionein

Five years ago, we published in Analytical Chemistry a paper describing a highly sensitive determination of a protein – metallothionein [5]. This in itself would not be anything special, if we had not also revealed that this low molecular weight, intracellular, cysteine-rich protein has a certain connection with a tumour disease in the subsequent experiments.

Is it a new possibility how we could diagnose a cancer?

As we have mentioned above, the sooner the cancer is detected, the better the chances to treat it successfully are. Thus, we used an electrochemical technique to analyse blood serum of patients with tumour diseases, the same way Brdicka did. Using a modified Brdicka reaction we have analyzed blood, blood serum and tumours of patients (more than 150) suffering from different types of cancers (melanoma, breast, lung, thyroid gland, kidney, oesophagus, large intestine, head and neck cancer, and leukaemia) and also blood and blood serum from non-cancer affected subjects. The results obtained show that the content of metallothionein increases markedly in blood and blood serum of the patients. We are the first scientific group in the world to not only quantify metallothionein in human blood serum, but also to report real differences between metallothionein levels of a control tissue and a tumourous one. Moreover, during thorough analysis of the experimental results obtained we found a unique correlation between the voltammogram data and the type of cancer. We called it an “electrochemical fingerprint”.

Could electrochemistry really be utilized for cancer diagnostics in the 21st century?

Could electrochemistry be used in 21st century in addition to other robust techniques such as mass spectrometry, nuclear magnetic resonance and many others? One could raise the objection that this “old technique” cannot compete with these modern methods, but in practice the contrary is the case. The results obtained show that electrochemical techniques could be brought back for the investigation of cancer and could potentially enable easy, fast and low cost cancer diagnostics. It is thus possible that the wishes of Jaroslav Heyrovsky and his follower and colleague Rudolf Brdicka will be fulfilled and this auspicious field of cancer study will be developed intensively, not only in Czech laboratories but also around the world.

Special issue “Utilization of Electrochemical Sensors and Biosensors in Biochemistry and Molecular Biology”

The special issue of Sensors contains more than thirty articles or reviews reporting on various fields of biological research. Experimental papers devoted to environmental stress at plants pay attention to the study of the influence of heavy metals on plant species and embryos. The most important feature of these papers was their multi-instrumental approach to find complex reactions of plants under stress [6-10]. Such a multi-instrumental approach was also employed in the paper reporting a non-destructive evaluation of historical papers [11].

Several papers report the use of miniaturized electrodes or miniaturized particles coupled with various detection techniques for the study of biochemical events and pathways [12-17]. As we mentioned at the beginning of this contribution, electrochemical techniques can be used in the diagnosis of tumour diseases [18, 19]. Moreover, these techniques can be also utilized for investigation of the interaction of anticancer drugs with various biologically active compounds, including glutathione, metallothionein and others [20, 21]. Attention was also paid to toxic substances such as bromadiolone, whch belongs to a group of second-generation anticoagulant rodenticides [22]. Other authors paid attention to the idea of using piezoelectric biosensors for a simple serological diagnosis of tularemia in hares [23]. Three papers were also published in which the authors used biochemical markers to study environmental pollution [24-26]. Similarly to these, new approaches and procedures to analyse cells and their behaviour were suggested [27].

Fruits and vegetables belong to the most important and crucial parts of human diet due to their health benefits. Plant tissues are rich in nutritionally or therapeutically active compounds, which are obviously products of plant secondary metabolism. Analysis of such compounds is therefore both important and needed. Moreover, new compounds belonging to the group of biologically active ones are continuosly being discovered. Sensor and biosensor research is also aimed at the developmenmt of easy-to-use and low cost detection of these substances [28-35].

Detection of nucleic acids is also of current interest, most of all due to recognition of their specific sequences. Approaches for studying nucleic acids, their interactions and modifications can differ, as shown in other papers published in the special issue [36-40].

Rene Kizek and Vojtech Adam would like to express their great thanks to Mr. Matthias Burkhalter, Dr. Shu-Kun Lin and others for their great support and for giving us the opportunity to prepare this Special Issue.

References1.BrdickaR.Application of the polarographic effect of proteins in cancer diagnosisNature19371393303302.BrdickaR.Polarographic investigations in serological cancer diagnosisNature1937139102010213.HeyrovskyJ.Polarographic research in cancerNature19381423173194.OlafsonR.W.SimR.G.Electrochemical approach to quantitation and characterization of metallothioneinsAnal. Biochem.19791003433515.KizekR.TrnkovaL.PalecekE.Determination of metallothionein at the femtomole level by constant current stripping chronopotentiometryAnal. Chem.200173480148076.SupalkovaV.HuskaD.DiopanV.HanustiakP.ZitkaO.StejskalK.BalounJ.PikulaJ.HavelL.ZehnalekJ.AdamV.TrnkovaL.BeklovaM.KizekR.Electroanalysis of plant thiolsSensors200779329597.SupalkovaV.PetrekJ.BalounJ.AdamV.BartusekK.TrnkovaL.BeklovaM.DiopanV.HavelL.KizekR.Multi-instrumental investigation of affecting of early somatic embryos of spruce by cadmium(II) and lead(II) ionsSensors200777437598.AdamV.BeklovaM.PikulaJ.HubalekJ.TrnkovaL.KizekR.Shapes of differential pulse voltammograms and level of metallothionein at different animal speciesSensors20077241924299.KrizkovaS.RyantP.KrystofovaO.AdamV.GaliovaM.BeklovaM.BabulaP.KaiserJ.NovotnyK.NovotnyJ.LiskaM.MalinaR.ZehnalekJ.HubalekJ.HavelL.KizekR.Multi-instrumental analysis of tissues of sunflower plants treated with silver(I) ions - Plants as bioindicators of environmental pollutionSensors2008844546310.RyantP.DolezelovaE.FabrikI.BalounJ.AdamV.BabulaP.KizekR.Electrochemical determination of low molecular mass thiols content in potatoes (Solanum tuberosum) cultivated in the presence of various sulphur forms and infected by late blight (Phytophora infestans)Sensors200883165318211.StrlicM.CigicI.K.KolarJ.de BruinG.PihlarB.Non-destructive evaluation of historical paper based on pH estimation from VOC emissionsSensors200773136314512.VestergaardM.KermanK.TamiyaE.An overview of label-free electrochemical protein sensorsSensors200773442345813.HubalekJ.HradeckyJ.AdamV.KrystofovaO.HuskaD.MasarikM.TrnkovaL.HornaA.KlosovaK.AdamekM.ZehnalekJ.KizekR.Spectrometric and voltammetric analysis of urease - nickel nanoelectrode as an electrochemical sensorSensors200771238125514.HuJ.Q.WangZ.P.LiJ.H.Gold nanoparticles with special shapes: Controlled synthesis, surface-enhanced Raman scattering, and the application in biodetectionSensors200773299331115.YogeswaranU.ChenS.M.A review on the electrochemical sensors and biosensors composed of nanowires as sensing materialSensors2008829031316.SatohW.HosonoH.YokomakuH.MorimotoK.UpadhyayS.SuzukiH.Integrated electrochemical analysis system with microfluidic and sensing functionsSensors200881111112717.WangY.XuH.ZhangJ.LiG.A Review of Electrochemical Sensors for Clinic AnalysisSensors200882043208118.AdamV.BalounJ.FabrikI.TrnkovaL.KizekR.An electrochemical detection of metallothioneins in nanolitres at zeptomole levelSensors200882293230519.KrizkovaS.FabrikI.AdamV.KukackaJ.PrusaR.ChavisG.J.TrnkovaL.StrnadelJ.HorakV.KizekR.Utilizing of adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum and tissuesSensors200883106312220.ZitkaO.HuskaD.KrizkovaS.AdamV.ChavisG.J.TrnkovaL.HornaA.HubalekJ.KizekR.An investigation of glutathione-platinum(II) interactions by means of the flow injection analysis using glassy carbon electrodeSensors200771256127021.AdamV.ZitkaO.DolezalP.ZemanL.HornaA.HubalekJ.SilenyJ.KrizkovaS.TrnkovaL.KizekR.Lactoferrin isolation using monolithic column coupled with spectrometric or micro-amperometric detectorSensors2008846448722.KrizkovaS.BeklovaM.PikulaJ.AdamV.HornaA.KizekR.Hazards of secondary bromadiolone intoxications evaluated using high-performance liquid chromatography with electrochemical detectionSensors200771271128623.PohankaM.TremlF.HubalekM.Band'ouchovaH.BeklovaM.PikulaJ.Piezoelectric biosensor for a simple serological diagnosis of tularemia in infected European brown hares (Lepus europaeus)Sensors200772825283424.HavelkovaM.RandakT.ZlabekV.KrijtJ.KroupovaH.PulkrabovaJ.SvobodovaZ.Biochemical markers for assessing aquatic contaminationSensors200772599261125.HuskaD.KrizkovaS.BeklovaM.HavelL.ZehnalekJ.DiopanV.AdamV.ZemanL.BabulaP.KizekR.Influence of cadmium(II) ions and brewery sludge on metallothionein level in earthworms (Eisenia fetida) - Biotransforming of toxic wastesSensors200881039104726.HavelkovaM.BlahovaJ.KroupovaH.RandakT.SlatinskaI.LeontovycovaD.GrabicR.PospisilR.SvobodovaZ.Biomarkers of contaminant exposure in Chub (Leuciscus cephalus L.) – a biomonitoring of major rivers in the Czech RepublicSensors200882589260327.ChoS.CastellarnauM.SamitierJ.ThieleckeH.Dependence of impedance of embedded single cells on cellular behaviourSensors200881198121128.AdamV.MikelovaR.HubalekJ.HanustiakP.BeklovaM.HodekP.HornaA.TrnkovaL.StiborovaM.ZemanL.KizekR.Utilizing of square wave voltammetry to detect flavonoids in the presence of human urineSensors200772402241829.KumarS.A.ChenS.M.Electroanalysis of NADH using conducting and redox active polymer/carbon nanotubes modified electrodes - A reviewSensors2008873976630.BelluzoM.S.RiboneM.E.LagierC.M.Assembling amperometric biosensors for clinical diagnosticsSensors200881366139931.GrieshaberD.MacKenzieR.VorosJ.ReimhultE.Electrochemical biosensors - Sensor principles and architecturesSensors200881400145832.ArvinteA.RotariuL.BalaC.Amperometric low-potential detection of malic acid using single-wall carbon nanotubes based electrodesSensors200881497150733.HuangF.PengY.Y.JinG.Y.ZhangS.KongJ.L.Sensitive detection of haloperidol and hydroxyzine at multi-walled carbon nanotubes-modified glassy carbon electrodesSensors200881879188934.MingL.XiX.ChenT.T.LiuJ.Electrochemical determination of trace Sudan I contamination in chili powder at carbon nanotube modified electrodesSensors200881890190035.MavrikouS.FlampouriK.MoschopoulouG.ManganaO.MichaelidesA.KintziosS.Assessment of Organophosphate and Carbamate Pesticide Residues in Cigarette Tobacco with a Novel Cell BiosensorSensors200882818283236.PanD.ZuoX.L.WanY.WangL.H.ZhangJ.SongS.P.FanC.H.Electrochemical interrogation of interactions between surface-confined DNA and methylene blueSensors200772671268037.Horakova-BrazdilovaP.FojtovaM.VytrasK.FojtaM.Enzyme-linked electrochemical detection of PCR-amplified nucleotide sequences using disposable screen-printed sensors. Applications in gene expression monitoringSensors2008819321038.HwangE.T.AhnJ.M.KimB.C.GuM.B.Construction of a nrdA :: luxCDABE fusion and its use in Escherichia coli as a DNA damage biosensorSensors200881297130739.de AbreuF.C.de PaulaF.S.FerreiraD.C.M.NascimentoV.B.SantosA.M.C.SantoroM.M.SalasC.E.LopesJ.C.D.GoulartM.O.F.The application of DNA-biosensors and differential scanning calorimetry to the study of the DNA-binding agent berenilSensors200881519153840.TrnkovaL.ZerzankovaL.DyckaF.MikelovaR.JelenF.Study of copper and purine-copper complexes on modified carbon electrodes by cyclic and elimination voltammetrySensors20088429444FiguresFigure 1.

Picture of plants cultivated in an environmental chamber under controlled conditions.